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Blog Post
Leukemia is a type of cancer that affects different types of stem cells that blood
cells. Leukemias can be acute (fast growing) or chronic (slower growing). Acute
myeloid leukemia (AML) is the most common acute leukemia in adults. Blood cells are
generated in the bone marrow, which is where AML starts in most cases. It can also
spread to other parts of the body including the lymph nodes, liver, spleen, central
nervous system (brain and spinal cord), and testicles, as explained by the American
Cancer Society.
IsoCode chip is one of a kind in carrying out single-cell assays to detect up to 30+
proteins secreted from live single immune cells, which allows precise assessment of
multifunctional, or polyfunctional capabilities of each immune cell type.
PSI score of single T cells was used by the scientists in the aforementioned study to
measure key cytokine markers indicating the 33% success rate of treatment in 16 AML
patients. They found that before treatment, bone marrow CD4+ but not CD8+ T cells
had significantly higher frequency of polyfunctional cells and significantly higher PSI
in patients who achieved complete remission (CR/CRi) compared with non-
responders. Five of 16 (31.2%) patients had achieved a CR/CRi on
azacitidine/nivolumab.
Other interesting findings included cytokines such as IFN-g and TNF-a were the major
drivers of enhanced PSI of pre-therapy CD4+ subset, whereas Granzyme B, IFN-g,
MIP1b and TNF-a drove the non-significantly enhanced pretreatment PSI of CD8+
subset, giving us an accurate picture of biomarker biology. Patients that responded to
the treatment also showed an increase in polyfunctional cell subsets with antitumor-
associated proteins in CD4+ and CD8+ subsets as compared with non-responders.
Pre-treatment PSI score provides us with a reliable metric to quantify treatment
outcome, which can be combined with other T-cell based strategies in clinical trials
for AML and other cancers. IsoPlexis’ single-cell proteomics functional detection
paves new pathways for solving unmet needs in cancer immunotherapy patient
biomarker profiling. This technology, as demonstrated by the prior study showing a
promising therapeutic response rate, has the potential to create powerful
breakthroughs in the anti-cancer drug discovery and diagnostics industry.
Sources:
Hussein Abbas, Zoe Alaniz, Sean G Mackay, Matthew Cyr, Jing Zhou, Ghayas C. Issa,
Mansour Alfayez, Jairo Matthews, Steven M Kornblau, Elias J Jabbour, Guillermo
Garcia-Manero, Marina Y Konopleva, Michael Andreeff, Naval G. Daver; Single-cell
Polyfunctional Proteomics of CD4 Cells from Patients with AML Predicts Responses to
Anti-PD-1-based therapy. Blood Adv 2021; bloodadvances.2021004583. doi:
https://doi.org/10.1182/bloodadvances.2021004583
Liu D., Paczkowski P., Mackay S., Ng C., Zhou J. (2020) Single-Cell Multiplexed
Proteomics on the IsoLight Resolves Cellular Functional Heterogeneity to Reveal
Clinical Responses of Cancer Patients to Immunotherapies. In: Thurin M., Cesano A.,
Marincola F. (eds) Biomarkers for Immunotherapy of Cancer. Methods in Molecular
Biology, vol 2055. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9773-2_19
Abhishek Maiti, Caitlin R. Rausch, Jorge E. Cortes, Naveen Pemmaraju, Naval G. Daver,
Farhad Ravandi, Guillermo Garcia-Manero, Gautam Borthakur, Kiran Naqvi, Maro
Ohanian, Nicholas J. Short, Yesid Alvarado, Tapan M. Kadia, Koichi Takahashi, Musa
Yilmaz, Nitin Jain, Steven Kornblau, Guillermo Montalban Bravo, Koji Sasaki, Michael
Andreeff, Prithiviraj Bose, Alessandra Ferrajoli, Ghayas C. Issa, Elias J. Jabbour, Lucia
Masarova, Philip A. Thompson, Sa Wang, Sergej Konoplev, Sherry A. Pierce, Jing Ning,
Wei Qiao, John S. Welch, Hagop M. Kantarjian, Courtney D. DiNardo, Marina Y.
Konopleva. Outcomes of relapsed or refractory acute myeloid leukemia after frontline
hypomethylating agent and venetoclax regimens. Haematologica 2020;106(3):894-898;
https://doi.org/10.3324/haematol.2020.252569.
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